4OKX

Crystal structure of W741L-AR-LBD bound with co-regulator peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 

Starting Model: experimental
View more details

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis.

Hsu, C.L.Liu, J.S.Wu, P.L.Guan, H.H.Chen, Y.L.Lin, A.C.Ting, H.J.Pang, S.T.Yeh, S.D.Ma, W.L.Chen, C.J.Wu, W.G.Chang, C.

(2014) Mol Oncol 8: 1575-1587

  • DOI: https://doi.org/10.1016/j.molonc.2014.06.009
  • Primary Citation of Related Structures:  
    4OEA, 4OED, 4OEY, 4OEZ, 4OFR, 4OFU, 4OGH, 4OH5, 4OH6, 4OHA, 4OIL, 4OIU, 4OJ9, 4OJB, 4OK1, 4OKB, 4OKT, 4OKW, 4OKX, 4OLM

  • PubMed Abstract: 

    Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR). Here, we found that anti-androgens-mt-ARs have similar binary structure to the 5α-dihydrotestosterone-wt-AR. Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and the AR. Functional studies showed that BUD31-related peptides suppressed AR transactivation, interrupted AR N-C interaction, and suppressed AR-mediated cell growth. Combination of peptide screening and X-ray structure analysis may serve as a new strategy for developing anti-ARs that simultaneously suppress both wt and mutated AR function.


  • Organizational Affiliation

    The George Whipple Lab for Cancer Research, Department of Pathology and Urology, University of Rochester Medical Center, Rochester, NY 14642, USA; Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 333, Taiwan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Androgen receptor250Homo sapiensMutation(s): 2 
Gene Names: ARDHTRNR3C4
UniProt & NIH Common Fund Data Resources
Find proteins for P10275 (Homo sapiens)
Explore P10275 
Go to UniProtKB:  P10275
PHAROS:  P10275
GTEx:  ENSG00000169083 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP10275
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
co-regulator peptide12N/AMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
198 BindingDB:  4OKX Ki: min: 11, max: 3700 (nM) from 4 assay(s)
IC50: min: 120.23, max: 2.46e+4 (nM) from 7 assay(s)
EC50: 1000 (nM) from 1 assay(s)
0U9 BindingDB:  4OKX Ki: min: 11, max: 2460 (nM) from 16 assay(s)
IC50: min: 10, max: 1.00e+5 (nM) from 36 assay(s)
EC50: min: 157, max: 1.00e+4 (nM) from 4 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.199 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.861α = 90
b = 66.674β = 90
c = 70.291γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-08-20
    Type: Initial release
  • Version 1.1: 2014-12-24
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description